Sex-specific effects of fetal exposure to the 1959-1961 Chinese famine on risk of adult hypertension.

Previous research is inconsistent about the effects of prenatal famine exposure on risk of adult hypertension. Follow-up of persons exposed to the 1959-1961 Chinese famine, the largest in human history, provides an opportunity to examine the long-term impact of prenatal famine exposure on adult cardiovascular disease (CVD). We investigated the effects of fetal-infant exposure to the famine on risk of hypertension in adulthood. We included 1,415 participants from the 2009 China Health and Nutrition Survey born September 1, 1956-December 31, 1964. Blood pressure (BP) measurements, self-reported previous diagnosis of hypertension and current anti-hypertension drug use were obtained from the survey. Differences in mean BP and risk of adult hypertension by famine exposure status were determined using linear and logistic regression analyses, after adjusting for confounders. Women with fetal-infant exposure to famine had higher mean systolic blood pressure (4.24 mmHg; 95% confidence interval (CI) 1.50-6.98) than those unexposed. They also had increased odds of a prior diagnosis of hypertension (odds ratio (OR) 2.16; 95% CI 1.16-4.02), and were more likely to be currently taking anti-hypertensive medications (OR 2.81; 95% CI 1.32-5.97) than unexposed women after adjusting for covariates. No statistically significant increases in mean BP or hypertension were seen among men. Exposure to famine during the fetal-infant period or early childhood has deleterious effects on adult health, but the effects may be greater for women. Gender-specific intervention strategies for CVD may be warranted for populations exposed to under-nutrition during critical time periods of fetal development.

Concordance of human papillomavirus types detected on the surface and in the tissue of genital lesions in men.

Swabbing the surface of a genital lesion to obtain a sample for HPV DNA testing is less invasive than a biopsy, but may not represent HPV types present in the lesion tissue. The objective of this study was to examine the concordance of HPV types detected in swab and biopsy samples from 165 genital lesions from men ages 18-70. Lesions included 90 condyloma, 10 penile intraepithelial neoplasia (PeIN), 23 non-condyloma with a known histology, and 42 lesions with an undetermined histology. All lesions were sampled by swabbing the surface of the lesion with a pre-wetted Dacron swab and taking a shave biopsy. HPV genotyping was performed using Linear Array for swab samples and INNO-LiPA for biopsy samples. The kappa and McNemar statistics were used to compare the concordance of detecting HPV types in swab and biopsy samples. Both sampling methods had high agreement for detection of HPV DNA in condyloma (87.8% agreement) and PeIN (100% agreement). There was also high concordance for detection of HPV16 (kappa = 1.00) and HPV18 (kappa = 1.00) in PeIN, however, agreement was low to moderate for detecting HPV6 (kappa = 0.31) and HPV11 (kappa = 0.56) in condyloma. Low to moderate agreement was also observed between sampling methods for detecting individual HPV types in the non-condyloma and lesions with an indefinite histology. The results suggest that obtaining a biopsy in addition to swabbing the surface of a lesion may provide additional information about specific HVP types associated with male genital lesions.

Risk factors for incident condyloma in a multinational cohort of men: the HIM study.

Identifying factors associated with condyloma are necessary for prevention efforts. Risk factors for incident condyloma were examined in a cohort of 2487 men from the United States, Brazil, and Mexico and were followed up every 6 months (median, 17.9 months). Factors strongly associated with condyloma were incident infection with human papillomavirus (HPV) types 6 and 11 (hazard ratio [HR], 12.42 [95% confidence interval {CI}, 3.78-40.77]), age (HR, 0.43 [95% CI, .26-.77]; 45-70 vs 18-30 years), high lifetime number of female partners (HR, 5.69 [95% CI, 1.80-17.97]; ≥21 vs 0 partners), and number of male partners (HR, 4.53 [95% CI, 1.68-12.20]; ≥3 vs 0 partners). The results suggest that HPV types 6 and 11 and recent sexual behavior are strongly associated with incident condyloma.

Sunlight exposure and cutaneous human papillomavirus seroreactivity in basal cell and squamous cell carcinomas of the skin.

BACKGROUND: Ultraviolet radiation exposure may interact synergistically with cutaneous human papillomavirus (HPV) infection in the development of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin. METHODS: To investigate differences in the risk of sunlight-associated BCC and SCC by cutaneous genus-specific HPV serostatus, a case-control study was conducted among 204 BCC and 156 SCC cases who were recruited from a university dermatology clinic and 297 controls who had no history of cancer and screened negative for current skin cancer. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between measures of sunlight exposure and BCC/SCC, stratified by genus-specific HPV serostatus, with adjustment for age and sex. RESULTS: Sunburn due to cutaneous sensitivity to sunlight exposure (P = .006) and poor tanning ability (P = .003) were associated with a higher seroprevalence for genus beta HPV types. Poor or no tanning ability was more strongly associated with SCC among individuals who were seropositive for antibodies to cutaneous HPV types in genera alpha (OR, 15.60; 95% CI, 5.40-45.1; P = .01 for interaction) and beta (OR, 6.86; 95% CI, 3.68-12.80; P = .001 for interaction), compared with individuals who were seronegative for these HPV types. CONCLUSIONS: Seropositivity for HPV types in genera alpha or beta increased the risk of SCC associated with poor tanning ability.

Patterns and timing of sunlight exposure and risk of basal cell and squamous cell carcinomas of the skin--a case-control study.

BACKGROUND: Non-melanoma skin cancer (NMSC), comprised of basal (BCC) and squamous (SCC) cell carcinomas, is the most common cancer in Caucasians. Ultraviolet radiation (UVR) exposure is the most important environmental risk factor for NMSC. However, the precise relationship between UVR and the risk of NMSC is complex, and the relationship may differ by skin cancer type. METHODS: A case-control study was conducted among Florida residents to investigate measures of patterns (intermittent vs. continuous) and timing (childhood vs. adulthood) of sunlight exposure in BCC and SCC. Participants included 218 BCC and 169 SCC cases recruited from a university dermatology clinic and 316 controls with no history of skin or other cancers. RESULTS: A history of blistering sunburn (a measure of intermittent sunlight exposure) was associated with both BCC (OR = 1.96, 95% CI = 1.27-3.03) and SCC (OR = 2.02, 95% CI = 1.22-3.33). Additionally, having a job in the sun for ≥ 3 months for 10 years or longer (a measure of continuous sunlight exposure) was also associated with both BCC and SCC in our study population. With the exception of younger age at first blistering sunburn, measures of younger age at sunlight exposure tended to be associated with SCC, but not BCC risk. CONCLUSIONS: Results from the current study suggest that sunlight exposure is associated with both BCC and SCC risk regardless of the pattern in which the exposure was received (i.e. intermittent vs. continuous). The data also suggest that sunlight exposure at a younger age may be more important for SCC but not BCC, however additional studies are needed to further characterize sunlight exposure-response relationships in different types of NMSC.

Incidence and human papillomavirus (HPV) type distribution of genital warts in a multinational cohort of men: the HPV in men study.

BACKGROUND: Data on the natural history of human papillomavirus (HPV)-related genital warts (GWs) in men are sparse. We described the distribution of HPV types in incident GWs and estimated GW incidence and time from type-specific incident HPV infections to GW detection in a multinational cohort of men aged 18-70 years. METHODS: Participants included 2487 men examined for GWs and tested for HPV every 6 months and followed up for a median of 17.9 months. Samples were taken from 112 men with incident GWs to test for HPV DNA by polymerase chain reaction. RESULTS: Incidence of GWs was 2.35 cases per 1000 person-years, with highest incidence among men aged 18-30 years (3.43 cases per 1000 person-years). HPV 6 (43.8%), HPV 11 (10.7%), and HPV 16 (9.8%) were the genotypes most commonly detected in GWs. The 24-month cumulative incidence of GWs among men with incident HPV 6/11 infections was 14.6% (95% confidence interval [CI], 7.5%-21.1%). Median time to GW detection was 17.1 months (95% CI, 12.4-19.3 months), with shortest time to detection among men with incident infections with HPV 6/11 only (6.2 months; 95% CI, 5.6-24.2 months). CONCLUSIONS: HPV 6/11 plays an important role in GW development, with the highest incidence and shortest time to detection among men with incident HPV 6/11 infection.

Patterns of care and outcomes among elderly individuals with primary malignant astrocytoma.

OBJECT: This study was undertaken to evaluate the association between age at diagnosis, patterns of care, and outcome among elderly individuals with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM). Methods Using the Surveillance, Epidemiology and End Results database, the authors identified 1753 individuals with primary GBM and 205 individuals with primary AA (diagnosed between June 1991 and December 1999) who were 66 years and older and whose records were linked to Medicare information. To facilitate gathering of prediagnosis comorbidity and postdiagnosis treatment information, only those individuals were included who had the same Medicare coverage for 6 months before and 12 months after diagnosis. The odds of undergoing various combinations of treatments and the associations with outcome were calculated by tumor type and age and adjusted by various predictors. RESULTS: Age was not associated with treatment differences in individuals with AA. Very elderly individuals (>or= 75 years old) with GBM were more likely to have biopsy only (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.78-3.59), surgery only (OR 1.47, 95% CI 1.15-1.87), or biopsy and radiation (OR 1.39, 95% CI 1.07-1.82) and were less likely to receive multimodal therapy. Regardless of patient age or lesion histological characteristics, survival was decreased in patients treated with biopsy only. Individuals with GBM who had surgery only or biopsy and radiation had worse outcomes than individuals treated with surgery and radiation. There were no differences in survival by lesion histological characteristics. Very elderly individuals with malignant astrocytomas were more likely to receive limited treatment (most pronounced in individuals with GBM). Survival variation correlated with treatment combinations. CONCLUSIONS: These findings suggest that in clinical neurooncology patient age is associated with not receiving effective therapies and hence worse prognosis.

Evaluation of adherence to national treatment guidelines among tuberculosis patients in three provinces of South Africa.

SETTING: Standardised tuberculosis (TB) treatment through directly observed therapy (DOT) is available in South Africa, but the level of adherence to standardised TB treatment and its impact on treatment outcomes is unknown. OBJECTIVES: To describe adherence to standardised TB treatment and provision of DOT, and analyse its impact on treatment outcome. METHODS: We utilised data collected for an evaluation of the South African national TB surveillance system. A treatment regimen was considered appropriate if based on national treatment guidelines. Multivariate log-binomial regression was used to evaluate the association between treatment regimens, including DOT provision, and treatment outcome. RESULTS: Of 1 339 TB cases in the parent evaluation, 598 (44.7%) were excluded from analysis owing to missing outcome or treatment information. The majority (697, 94.1%) of the remaining 741 patients received an appropriate TB regimen. Almost all patients (717, 96.8%) received DOT, 443 (59.8%) throughout the treatment course and 274 (37.0%) during the intensive (256, 34.6%) or continuation (18, 2.4%) phase. Independent predictors of poor outcome were partial DOT (adjusted risk ratio (aRR) 3.1, 95% confidence interval (CI) 2.2 - 4.3) and previous treatment default (aRR 2.3, 95% CI 1.1 - 4.8). CONCLUSION: Patients who received incomplete DOT or had a history of defaulting from TB treatment had an increased risk of poor outcomes.

Prevalent serum antibody is not a marker of immune protection against acquisition of oncogenic HPV16 in men.

In women, naturally induced anti-human papilloma virus (HPV) serum antibodies are a likely marker of host immune protection against subsequent HPV acquisition and progression to precancerous lesions and cancers. However, it is unclear whether the same is the case in men. In this study, we assessed the risk of incident genital infection and 6-month persistent genital infection with HPV16 in relation to baseline serostatus in a cohort of 2,187 men over a 48-month period. Genital swabs were collected every 6 months and tested for HPV presence. Incidence proportions by serostatus were calculated at each study visit to examine whether potential immune protection attenuated over time. Overall, incidence proportions did not differ statistically between baseline seropositive and seronegative men at any study visit or over the follow-up period. The risk of incident and 6-month persistent infection was not associated with baseline serostatus or baseline serum antibody levels in the cohort. Our findings suggest that baseline HPV seropositivity in men is not associated with reduced risk of subsequent HPV16 acquisition. Thus, prevalent serum antibodies induced by prior infection may not be a suitable marker for subsequent immune protection against genital HPV16 acquisition in men.

Human papillomavirus (HPV) 6, 11, 16, and 18 seroprevalence is associated with sexual practice and age: results from the multinational HPV Infection in Men Study (HIM Study).

BACKGROUND: Few human papillomavirus (HPV) serology studies have evaluated type-specific seroprevalence of vaccine HPV types in men. This study investigates seroprevalence of HPV 6, 11, 16, and 18, and associated risk factors in men residing in three countries (United States, Mexico, and Brazil). METHODS: Data from 1,477 men aged 18 to 70 enrolled in the HPV Infection in Men Study (HIM Study) were analyzed. Serum antibody testing was performed with virus-like particle-based ELISA. Potential risk factors were assessed for individual HPV types by the use of logistic regression. RESULTS: Overall, HPV-6, 11, 16, and 18 seroprevalence was 14.8%, 17.3%, 11.2%, and 5.8%, respectively. Thirty-four percent of men were seropositive to one or more HPV types. When examined by sexual practice, 31.2% of men who had sex with women, 65.6% of men who had sex with men (MSM), and 59.4% of men who had sex with both men and women (MSMW) were seropositive to one or more HPV types. Seroprevalence increased with age among young-to-middle-aged men with significant upward age trends observed for HPV 11, 16, and 18. Men with multiple lifetime male anal sex partners were 2 to 4 times more likely to be HPV 6 or 11 seropositive and 3 to 11 times more likely to be HPV 16 or 18 seropositive. CONCLUSION: Our data indicate that exposures to vaccine HPV types were common in men and highly prevalent among MSM and MSMW. IMPACT: Our study provides strong evidence that the practice of same-sex anal intercourse is an independent risk factor for seroprevalence of individual vaccine HPV types. Examination of antibody responses to HPV infections at various anatomic sites in future studies is needed to elaborate on the mechanism.

Inherited variants in mitochondrial biogenesis genes may influence epithelial ovarian cancer risk.

BACKGROUND: Mitochondria contribute to oxidative stress, a phenomenon implicated in ovarian carcinogenesis. We hypothesized that inherited variants in mitochondrial-related genes influence epithelial ovarian cancer (EOC) susceptibility. METHODS: Through a multicenter study of 1,815 Caucasian EOC cases and 1,900 controls, we investigated associations between EOC risk and 128 single nucleotide polymorphisms (SNPs) from 22 genes/regions within the mitochondrial genome (mtDNA) and 2,839 nuclear-encoded SNPs localized to 138 genes involved in mitochondrial biogenesis (BIO, n = 35), steroid hormone metabolism (HOR, n = 13), and oxidative phosphorylation (OXP, n = 90) pathways. Unconditional logistic regression was used to estimate OR and 95% CI between genotype and case status. Overall significance of each gene and pathway was evaluated by using Fisher's method to combine SNP-level evidence. At the SNP level, we investigated whether lifetime ovulation, hormone replacement therapy (HRT), and cigarette smoking were confounders or modifiers of associations. RESULTS: Interindividual variation involving BIO was most strongly associated with EOC risk (empirical P = 0.050), especially for NRF1, MTERF, PPARGC1A, ESRRA, and CAMK2D. Several SNP-level associations strengthened after adjustment for nongenetic factors, particularly for MTERF. Statistical interactions with cigarette smoking and HRT use were observed with MTERF and CAMK2D SNPs, respectively. Overall variation within mtDNA, HOR, and OXP was not statistically significant (empirical P > 0.10). CONCLUSION: We provide novel evidence to suggest that variants in mitochondrial biogenesis genes may influence EOC susceptibility. IMPACT: A deeper understanding of the complex mechanisms implicated in mitochondrial biogenesis and oxidative stress may aid in developing strategies to reduce morbidity and mortality from EOC.

LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer.

Defective microRNA (miRNA) biogenesis contributes to the development and progression of epithelial ovarian cancer (EOC). In this study, we examined the hypothesis that single nucleotide polymorphisms (SNP) in miRNA biogenesis genes may influence EOC risk. In an initial investigation, 318 SNPs in 18 genes were evaluated among 1,815 EOC cases and 1,900 controls, followed up by a replicative joint meta-analysis of data from an additional 2,172 cases and 3,052 controls. Of 23 SNPs from 9 genes associated with risk (empirical P < 0.05) in the initial investigation, the meta-analysis replicated 6 SNPs from the DROSHA, FMR1, LIN28, and LIN28B genes, including rs12194974 (G>A), an SNP in a putative transcription factor binding site in the LIN28B promoter region (summary OR = 0.90, 95% CI: 0.82-0.98; P = 0.015) which has been recently implicated in age of menarche and other phenotypes. Consistent with reports that LIN28B overexpression in EOC contributes to tumorigenesis by repressing tumor suppressor let-7 expression, we provide data from luciferase reporter assays and quantitative RT-PCR to suggest that the inverse association among rs12194974 A allele carriers may be because of reduced LIN28B expression. Our findings suggest that variants in LIN28B and possibly other miRNA biogenesis genes may influence EOC susceptibility.

Epidemiologic factors associated with seropositivity to human papillomavirus type 16 and 18 virus-like particles and risk of subsequent infection in men.

Our understanding of humoral response to human papillomavirus (HPV) infection has been mainly derived from studies in women. The role of serum antibodies in the natural history of HPV in men has yet to be investigated. Data from 285 male participants of a natural history study were used to determine the epidemiologic factors associated with HPV 16/18 seropositivity and explore the role of HPV 16 and 18 serum antibodies in subsequent HPV infections. Serum antibodies were detected by use of HPV 16- and 18 virus-like particles enzyme-linked immunoassay. Logistic regression and Generalized Estimating Equation was used for the evaluation of risk factors. The risk of subsequent HPV infection by baseline antibody status was assessed by incidence rate ratio and its confidence intervals. Men ages 36 to 44 years compared with men ages 18 to 25 years were four times more likely to be seropositive to HPV 16/18. In addition, being divorced, separated, or widowed; being a former smoker; and having sex with men was positively and independently associated with HPV 16/18 seropositivity. Our findings on the potential role of HPV 16 or 18 serum antibodies in subsequent infection were inconclusive. Large prospective studies are warranted to adequately address questions on the role of natural immunity in the natural history of HPV infections in men.